Treatment with Volanesorsen, a 2'-O-Methoxyethyl-Modified Antisense Oligonucleotide Targeting APOC3 mRNA, Does Not Affect the QTc Interval in Healthy Volunteers.

ABSTRACT: The aim of this study was to assess the effect of volanesorsen on the corrected QT (QTc) interval. This thorough QT study enrolled 52 healthy male and female subjects who were randomized at a single site in a four-way crossover study. Subjects were randomly assigned to 1 of 12 treatment sequences and crossed over into four treatment periods over the course of which each subject was to receive a single therapeutic dose of volanesorsen as a 300?mg subcutaneous (SC) injection, a single supratherapeutic dose of volanesorsen as 300?mg intravenous (IV) infusion, a single oral (PO) dose of moxifloxacin (positive control), and placebo dose. The study demonstrated that volanesorsen 300?mg SC and 300?mg IV did not have a clinically relevant effect on ??QTcF exceeding 10?ms. The largest mean effect at any postdose time point was 3.0?ms (90% confidence interval [CI]: 0.8-5.2) after SC dosing and 1.8?ms (90% CI -0.4 to 4.0) after IV dosing. Volanesorsen, at the studied therapeutic and supratherapeutic doses, does not have a clinically meaningful effect on the QTc.

SUBMITTER: Watts LM 

PROVIDER: S-EPMC7415887 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature